Human embryonic stem cells (hESC) as a source of insulin-producing cells

Abstract Purpose of review: Pancreas and islet transplantation provide proof-of-principle that replacing deficient β cell function in patients with insulin-dependent diabetes can restore normoglycemia. The dearth of suitable cadaver organs and need for lifelong immunosuppression, however, limit this therapy to only a few thousand individuals. Therapeutic strategies involving human pluripotent stem cell-derived insulin-producing cells (IPCs) and tissues have long been envisioned as a potential solution to this clinical problem. Recent technical advances in deriving IPCs with improved functionality are bringing this vision closer to reality. Transplanting endocrine progenitors contained in macroencapsulation devices is a strategy that has already entered clinical trials. Many questions still need to be answered related to cellular properties, composition and immunogenicity of the graft and how to protect the graft from immune destruction, as well as transplant site and the role of other tissue components such as extracellular matrix. Exciting new technologies such as tissue engineering, genome editing, and interspecies organogenesis are already impacting this field and will likely contribute to the ultimate delivery of stem cell-derived IPCs to patients. This chapter will review the current state of the preclinical technology and review results of a recent industry-sponsored first-in-human clinical trial.